Triethylamine → 7-(1-tert-Butoxycarbonylamino-6-azaspiro[2.5]oct-6-yl)-6-fluoro-1-(2,4-difluorophenyl)-1,4-dihydro-4-oxo-1,8-naphthyridine-3-carbOxylic acid, ethyl ester

HRID 1654514Notes

Reaction equation

HRID 1654514 reaction equation
[C:1]([O:5][C:6]([NH:8][CH:9]1[C:11]2([CH2:16][CH2:15][NH:14][CH2:13][CH2:12]2)[CH2:10]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].Cl[C:18]1[N:27]=[C:26]2[C:21]([C:22](=[O:39])[C:23]([C:36]([OH:38])=[O:37])=[CH:24][N:25]2[C:28]2[CH:33]=[CH:32][C:31]([F:34])=[CH:30][C:29]=2[F:35])=[CH:20][C:19]=1[F:40].[CH2:41](N(CC)CC)[CH3:42].C(OCC)(=O)C.CCCCCC>C(#N)C.C(OCC)(=O)C.CCCCCC.CO>[C:1]([O:5][C:6]([NH:8][CH:9]1[C:11]2([CH2:12][CH2:13][N:14]([C:18]3[N:27]=[C:26]4[C:21]([C:22](=[O:39])[C:23]([C:36]([O:38][CH2:41][CH3:42])=[O:37])=[CH:24][N:25]4[C:28]4[CH:33]=[CH:32][C:31]([F:34])=[CH:30][C:29]=4[F:35])=[CH:20][C:19]=3[F:40])[CH2:15][CH2:16]2)[CH2:10]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 105460847-Chloro-1-(2,4-difluorophenyl)-6-fluoro-4-oxo-1,4-dihydro-1,8-naphthyridine-3-carboxylic acidHCID 15282171tert-Butyl 6-azaspiro[2.5]octan-1-ylcarbamateHCID 21226206Ethyl acetate hexane

Product 1

HCID 152821727-(1-tert-Butoxycarbonylamino-6-azaspiro[2.5]oct-6-yl)-6-fluoro-1-(2,4-difluorophenyl)-1,4-dihydro-4-oxo-1,8-naphthyridine-3-carbOxylic acid, ethyl esterYield 86%

Reagents, catalysts & solvents 2

HCID 6342AcetonitrileSolventHCID 21879739Ethyl acetate hexane methanolSolvent

Procedure

A solution of 1-tert-butoxycarbonylamino-6-azaspiro[2.5]octane (250 mg, 1.11 mmol), the ethyl ester of 7-chloro-6-fluoro-1-(2,4-difluorophenyl)-1,4-dihydro-4-oxo-1,8-naphthyridine-3-carboxylic acid (382 mg, 1.00 mmol) and triethylamine (0.78 ml, 5.55 mmol) in acetonitrile (15 ml) was heated at reflux overnight. Solvent was removed in vacuo and the residue was chromatographed on silica gel (eluents: 50% ethyl acetate/hexane, then 5:5:1 ethyl acetate/hexane/methanol) to afford the title product as an off-white solid (494 mg, 0.86 mmol, yield 86%).

Workup

  1. temperatureat reflux overnight
  2. customSolvent was removed in vacuo
  3. customthe residue was chromatographed on silica gel (eluents

Sources & evidence

ORD record
ord-a71b47f913864fcda7384169f9095f30
Source dataset
uspto-grants-1995_04
Patent number
US05407943

Reaction notes

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